We propose to develop high-resolution microwave-induced thermoacoustic tomography (TAT) and laser-induced photoacoustic tomography (PAT) by adapting a clinical ultrasound imaging system. These three compatible imaging modalities share the same ultrasound detection system and provide complementary contrasts. The long-term goal is to provide a clinical tool for the early functional monitoring of breast neoadjuvant therapy (chemo- or hormone therapy). Many breast cancer patients receive neoadjuvant treatment to reduce tumor size and enable breast conserving therapy that would otherwise have not been possible. A sensitive method of detecting response to therapy might allow earlier adjustments in treatment, and thus, result in better outcomes. Furthermore, if drug choices are not resulting in response, prompt and early changes in drug regimens will alleviate some of the unnecessary morbidity that patients suffer during treatment while awaiting response to therapy. TAT/PAT is based on the generation of thermoacoustic/photoacoustic waves by the safe deposition of short-pulsed electromagnetic energy into the breast. Each microwave/laser pulse causes a rapid temperature rise on the order of 10 millidegrees. The ultrasonic emission due to thermoelastic expansion is detected with an array of ultrasonic transducers and then used to reconstruct an image. TAT and PAT are designed to overcome the poor spatial resolution of pure microwave and pure optical imaging yet to retain the high contrasts. In terms of spatial resolution, pure microwave imaging suffers from strong diffraction due to long microwave wavelength, whereas pure optical imaging suffers from strong optical scattering in tissue. Ultrasonic waves can propagate in tissue with relatively low scattering and can therefore provide good spatial resolution. The applicants have demonstrated speckle-free images at high resolution (as low as 0.5 mm). We hypothesize that the combined contrasts from TAT and PAT as well as ultrasonography can accurately predict breast neoadjuvant therapeutic response. TAT measures dominantly water/sodium contrast, whereas PAT measures blood volume and blood oxygenation contrasts. The specific aims are as follows: 1. Development of the TAT/PAT breast imaging system. 2. Adaptation of a Philips clinical ultrasound imaging system. 3. Phantom study: Validate the proposed imaging system with tissue phantoms. 4. In vivo study: First, image a small number of human breasts to fine tune the imaging system. Second, image human breasts and perform statistical analysis retrospectively. Third, image human breasts and validate the imaging system prospectively. PUBLIC HEALTH RELEVANCE: Imaging technologies have enabled numerous discoveries in biomedicine and provided early diagnosis of disease. Functional imaging that detects not only tissue structure but also tissue function will make even greater impact in biomedicine. The proposed thermoacoustic and photoacoustic imaging technologies can potentially provide a clinical tool for the early functional monitoring of breast neoadjuvant therapy (chemo- or hormone therapy).